DESCRIPTION (applicant's abstract): The long-term goal of this project is to examine the early development of key neuropeptides and receptors involved in energy homeostasis using the model of diet-induced obesity (DIO). While alterations in the expression of neuropeptides involved in energy homeostasis have been identified in single-gene rodent models of obesity, these do not accurately typify human obesity, which appears to be polygenic. Since the rat model of DIO and human obesity share a number of traits, understanding the factors that predate (and therefore may contribute to) DIO in rodents may offer insight into human obesity. Using a unique rat model of DIO in which the propensity to become obese (DIO) or resist obesity (DR) on an energy-dense diet is known from conception, this proposal will determine 1) the ontogeny of hypothalamic expression of NPY, AGRP, POMC, and the leptin receptor (Ob-Rb) in selectively bred DIO-prone and DR-prone rat pups in association with the development of ingestive behavior and adiposity; 2) the effects of leptin administration on ARC SOCS-3, NPY, AGRP and POMC expression and body weight in selectively bred DIO- and DR-prone rats and 3) the effect of manipulating the pre- and post-natal environment on the development of the selectively-bred DIO and DR phenotypes. These experiments will provide a more complete understanding of the neural and endocrine systems involved in the development and perpetuation of obesity.